Bio-Medical Materials and Engineering - Volume 28, issue s1

Authors: Ducret, Maxime | Fabre, Hugo | Celle, Alexis | Mallein-Gerin, Frédéric | Perrier-Groult, Emeline | Alliot-Licht, Brigitte | Farges, Jean-Christophe

Article Type: Research Article

Abstract: Tooth vitality and health are related to the presence of a living connective tissue, the dental pulp (DP), in the center of the dental organ. The DP contains the tooth immune defence system that is activated against invading oral cariogenic bacteria during the caries process and the tissue repair/regeneration machinery involved following microorganisms’ eradication. However, penetration of oral bacteria into the DP often leads to complete tissue destruction and colonization of the endodontic space by microorganisms. Classical endodontic therapies consist of disinfecting then sealing the endodontic space with a gutta percha-based material. However, re-infections of the endodontic space by oral …bacteria can occur, owing to the lack of tightness of the material. Recent findings suggest that regenerating a fully functional pulp tissue may be an ideal therapeutic solution to maintain a tooth defence system that will detect and help manage future injuries. The objective of this paper was to explain the different revascularization and regeneration strategies that have been proposed to reconstitute a living DP tissue and to discuss the main challenges that have to be resolved to improve these therapeutic strategies. Show more

Keywords: Human tooth, dental pulp regeneration, revascularization, mesenchymal stem cells, cell-based medicinal products

DOI: 10.3233/BME-171637

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S159-S168, 2017

Authors: Wagner, Delphine | Bolender, Yves | Rémond, Yves | George, Daniel

Article Type: Research Article

Abstract: Although orthodontics have greatly improved over the years, understanding of its associated biomechanics remains incomplete and is mainly based on two dimensional (2D) mechanical equilibrium and long-time clinical experience. Little experimental information exists in three dimensions (3D) about the forces and moments developed on orthodontic brackets over more than two or three adjacent teeth. We define here a simplified methodology to quantify 3D forces and moments applied on orthodontic brackets fixed on a dental arch and validate our methodology using existing results from the literature by means of simplified hypotheses.

Keywords: Orthodontic, tooth movement, force, moment, friction, periodontium

DOI: 10.3233/BME-171638

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S169-S177, 2017

Authors: Wagner, Delphine | Bolender, Yves | Rémond, Yves | George, Daniel

Article Type: Research Article

Abstract: Orthodontic appliances deliver forces and moments that will determine movement of teeth. To analyze this latter, we developed an experimental setup to measure the mechanical forces applied on the teeth and to calculate, through a simplified theoretical analysis, the reactive forces and corresponding moments onto the brackets of three adjacent teeth. To validate the theoretical and experimental results, we use a simplified clinical situation of a maxillary canine in infraclusion and surrounded by its corresponding upper lateral incisor and first premolar. Forces are then measured experimentally and compared with the calculated results. From this, we show the specific dissymmetry of …the mechanical forces on each side of the maxillary canine due to the applied mechanical forces and the undesirable induced generated moments occurring on each tooth that will directly impact the bone remodeling process and the final tooth repositioning. Show more

Keywords: Orthodontics, dental arch, periodontium, bone remodeling

DOI: 10.3233/BME-171639

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S179-S184, 2017

Authors: Offner, Damien | Wagner, Quentin | Idoux-Gillet, Ysia | Gegout, Hervé | Ferrandon, Arielle | Schwinté, Pascale | Musset, Anne-Marie | Benkirane-Jessel, Nadia | Keller, Laetitia

Article Type: Research Article

Abstract: The time needed to obtain functional regenerated bone tissue depends on the existence of a reliable vascular support. Current techniques used in clinic, for example after tooth extraction, do not allow regaining or preserving the same bone volume. Our aim is to develop a cellularized active implant of the third generation, equipped with human mesenchymal stem cells to improve the quality of implant vascularization. We seeded a commercialized collagen implant with human mesenchymal stem cells (hMSCs) and then with human umbilical vein endothelial cells (HUVECs). We analyzed the biocompatibility and the behavior of endothelial cells with this implant. We observed …a biocompatibility of the active implant, and a re-organization of endothelial cells into clustered networks. This work shows the possibility to develop an implant of the third generation supporting vascularization, improving the medical care of patients. Show more

Keywords: Collagen implant, vascularization, mesenchymal stem cells, endothelial cells

DOI: 10.3233/BME-171640

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S185-S192, 2017

Authors: Yu, Hao | Cauchois, Ghislaine | Louvet, Nicolas | Chen, Yun | Rahouadj, Rachid | Huselstein, Céline

Article Type: Research Article

Abstract: Once articular cartilage is damaged, it has poor ability to heal. At present, alginate-based hydrogels have 3D-dimensional physical structures with great potential for applications in carilage tissue engineering. For osteochondral defect, it will be necessary to use stratified scaffold to mimic zonal organization of cartilage. This study aims to compare the characteristics of alginate (Alg)/hyaluronic acid (HA) hydrogels which will mimic cartilage with alginate (Alg)/hydroxyapatite (Hap) hydrogels which will mimic subchondral bone. In this work, we fabricated the 3D-Alg/HA and Alg/Hap hydrogel scaffolds by the original spraying method. From the physical-mechanical properties, we compared mechanical behaviour of Alg/HA and Alg/Hap …hydrogel scaffolds, which were examined using indentation testing and viscosity behaviour. This results showed that the Alg/Hap hydrogels exhibited a relative high mechanical strength, as well as the viscosity of Alg/Hap hydrogels is slight slower than Alg/HA hydrogels. However, autoclaving has more deleterious effect on the mechanical and viscosity properties of Alg/HA and Alg/Hap hydrogels. Cytotoxicity was evaluated through the culture of hydrogel beads-laden Wharton’s jelly mesenchymal stem cells (WJ-MSC). In addition, the chondrogenic differentiation of WJ-MSC encapsulated into Alg/HA and Alg/Hap hydrogels were performed by histological analyzing during 30 days of culture. From these results, the percentage of living cells for Alg/Hap is significantly higher than Alg/HA, which also is associated with the results of shear viscosity. Both of hydrogels exhibited differentiate into chondrocyte matrix as collagen and proteoglycans. In conclusion, Alg/Hap hydrogels presented better mechanical property, cytocompatibility and differentiation characteristics than Alg/HA hydrogels. Show more

Keywords: Alginate, hyaluronic acid, hydroxyapatite, Wharton’s jelly mesenchymal stem cells, mechanical properties

DOI: 10.3233/BME-171641

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S193-S200, 2017

Authors: Cucchiarini, Magali

Article Type: Research Article

Abstract: Articular cartilage injuries have an inadequate aptitude to reproduce the original structure and functions of this highly specialized tissue. As most of the currently available options also do not lead to the restoration of the original hyaline cartilage, novel treatments are critically needed to address this global problems in the clinics. Gene therapy combined with tissue engineering approaches offers effective tools capable of enhancing cartilage repair experimentally, especially those based on the controlled delivery of the highly effective, clinically adapted recombinant adeno-associated viral (rAAV) vectors. This work presents an overview of the most recent evidence showing the benefits of using …rAAV vectors and biocompatible materials for the elaboration of adapted treatments against cartilage injuries. Show more

Keywords: rAAV vectors, articular cartilage, tissue engineering, repair

DOI: 10.3233/BME-171642

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S201-S207, 2017

Authors: Comblain, Fanny | Rocasalbas, Guillem | Gauthier, Sandrine | Henrotin, Yves

Article Type: Research Article

Abstract: Osteoarthritis (OA) is a painful, degenerative and inflammatory disease that affects the entire synovial joints. Nowadays, no cure exists, and the pharmacological treatments are limited to symptoms alleviation. There is a need for a new efficient and safe treatment. Viscosupplementation is a process that aims to restore the normal rheological properties of synovial fluid. For the past years, hyaluronic acid was usually used but this molecule has some limitations including the short residency time in joint cavity. Recently, in vitro studies have suggested that chitosan could promote the expression of cartilage matrix components and reduce inflammatory and catabolic mediator’s …production by chondrocytes. In vivo , chitosan prevented cartilage degradation and synovial membrane inflammation in OA induced rabbit model. Several studies have also shown that chitosan could induce chondrogenic differentiation of mesenchymal stem cells. Therefore, chitosan is an interesting polymer to design scaffold and hydrogel for cartilage lesion repair, cells transplantation, sustained drug release and viscosupplementation. Show more

Keywords: Chitosan, viscosupplementation, tissue engineering, cartilage repair, stem cells

DOI: 10.3233/BME-171643

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S209-S215, 2017

Authors: Yang, Xu | Qi, Yongjian | Avercenc-Leger, Léonore | Vincourt, Jean-Baptiste | Hupont, Sébastien | Huselstein, Céline | Wang, Hui | Chen, Liaobin | Magdalou, Jacques

Article Type: Research Article

Abstract: Background: Osteoarthritis (OA) is a chronic joint disease characterized by a progressive and irreversible degeneration of articular cartilage. Among the environmental risk factors of OA, tobacco consumption features prominently, although, there is a great controversy regarding the role of tobacco smoking in OA development. Among the numerous chemicals present in cigarette smoke, nicotine is one of the most physiologically active molecules. Objective: The aim of the study was (i) to measure the impact of nicotine on the proliferation and chondrogenic differentiation of mesenchymal stem cells from the human Wharton’s jelly (hWJ-MSCs) into chondrocytes, (ii) to investigate whether the …α 7 nicotinic acetylcholine receptors (nAChRs) was expressed in hWJ-MSCs and could play a role in the process. The project benefits from the availability of an umbilical cord bank from which hWJ-MSCs were originated. Methods: The hWJ-MSCs were cultured and used up to passage 5. The proliferation of hWJ-MSCs with 5 μ M nicotine was measured by the MTT assay on the 1st, 2nd, 3rd, and 6th day. Flow cytometry analysis was used to detect cell apoptosis/necrosis by Annexin V/PI double-staining. The chondrogenic differentiation grade of hWJ-MSCs induced by TGFβ 3 was assessed by the Sirius red and Alcian blue staining. The expression of markers genes was followed by quantitative real-time PCR. The expression of nAChRs was followed by RT-PCR. The functional activity of α 7 nAChR was evaluated by calcium (Ca2+ ) influx mediated by nicotine using the Fluo-4 NW Calcium assay. Results: The proliferation of hWJ-MSCs was significantly impaired by nicotine (5 μ M) from the 3rd day of treatment, but nicotine did not significantly induce modifications on the viability of hWJ-MSCs. Alcian blue staining indicated that the amount of proteoglycan was more abundant in control group than in the nicotine group, but no difference was observed on the total collagen amount using Sirius red staining. The mRNA expression of Sox9, type II collagen (Col2a1), aggrecan in control group was higher than in the nicotine group. We found that hWJ-MSCs expressed α 7 nAChR. The receptor agonist nicotine caused calcium (Ca2+ ) influx into hWJ-MSCs suggesting that the calcium ion channel α 7 homopolymer could mediate this response. Conclusions: At the concentration used, nicotine had an adverse effect on the proliferation and chondrogenic differentiation of hWJ-MSCs which was probably impaired through a α 7 nAChR mediation. Show more

Keywords: Nicotine, human Wharton’s jelly mesenchymal stem cells, chondrogenic differentiation, nicotinic acetylcholine receptor, osteoarthritis

DOI: 10.3233/BME-171644

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S217-S228, 2017

Authors: Henrionnet, Christel | Dumas, Dominique | Hupont, Sébastien | Stoltz, Jean François | Mainard, Didier | Gillet, Pierre | Pinzano, Astrid

Article Type: Research Article

Abstract: In tissue engineering approaches, the quality of substitutes is a key element to determine its ability to treat cartilage defects. However, in clinical practice, the evaluation of tissue-engineered cartilage substitute quality is not possible due to the invasiveness of the standard procedure, which is to date histology. The aim of this work was to validate a new innovative system performed from two-photon excitation laser adapted to an optical macroscope to evaluate at macroscopic scale the collagen network in cartilage tissue-engineered substitutes in confrontation with gold standard histologic techniques or immunohistochemistry to visualize type II collagen. This system permitted to differentiate …the quality of collagen network between ITS and TGF-β 1 treatments. Multiscale large field imaging combined to multimodality approaches (SHG-TCSPC) at macroscopical scale represent an innovative and non-invasive technique to monitor the quality of collagen network in cartilage tissue-engineered substitutes before in vivo implantation. Show more

Keywords: Cartilage, tissue-engineered substitute, second harmonic generation, mesenchymal stem cells

DOI: 10.3233/BME-171645

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S229-S235, 2017

Authors: Luo, Bin | Yu, Zhui | Li, Yinping

Article Type: Research Article

Abstract: Sepsis is a systemic inflammatory response syndrome with high mortality, which results from severe infection and can lead to secondary organ dysfunction. It is one of the most common cause of death in intensive care unit. Clinical reports have shown that sepsis was often accompanied by thyroid dysfunction, which is called “low triiodothyronine (T3)” syndrome and characterized by decreased blood total T3 and free T3, and by normal or decreased thyroxine (T4) and thyroid stimulating hormone (TSH). This syndrome may greatly affect the prognosis of patients with sepsis. The main purpose of this review is to illustrate the role of …thyroid hormone disorder in the development and prognosis of sepsis. Show more

Keywords: Sepsis, thyroid hormone, low T3 syndrome, organ dysfunction

DOI: 10.3233/BME-171646

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S237-S241, 2017

Authors: Yu, Fang | Xu, Jian | Xiao, Zheman | Peng, Biwen | He, Xiaohua

Article Type: Research Article

Abstract: Background: KCNQ2 plays a key role in the regulation of neuronal excitability. The R214W and Y284C mutants of KCNQ2 channels, which are associated with BFNC, can decrease channel function to cause neuronal hyperexcitability and promote seizures. Previous studies revealed that elevated temperature caused up-regulation of KCNQ2 expression. Objective: The present study sought to investigate the impact of temperature elevation on neuronal KCNQ2 ion channel mutants. Methods: Protein expression of wt KCNQ2 and the R214W, Y284C and truncated selective filter mutants at different temperatures was detected by live-cell confocal fluorescence microscopy and by Western blotting. Whole-cell patch …clamp was performed to record the effect of temperature on the electrophysiological activity of KCNQ2 channels. Results: Temperature elevation caused an unexpected increase in voltage-dependent KCNQ2 channel activation but also increased the endoplasmic reticulum (ER) retention of KCNQ2 protein, and the ER retention was greater for mutants associated with BFNC than for wt KCNQ2. Temperature elevation did not increase the fluorescence intensity of cells transfected with a truncated selective filter mutant. Conclusions: The direct effect of heat on KCNQ2 channels may be involved in excitability regulation of neurons, and the P-loop region is critical for temperature-dependent modulation of the expression and trafficking of KCNQ2 channels. Show more

Keywords: KCNQ2, ion channels, temperature, febrile seizures, benign familial neonatal convulsions

DOI: 10.3233/BME-171647

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S243-S253, 2017

Authors: Wu, Yu | Yao, Xihui | Chen, Yun | Li, Yinping | Tian, Weiqun

Article Type: Research Article

Abstract: Development of smart and functional polymeric carriers, which enable controlled or timed release of a bioactive material, thereby providing a better dosing pattern and minimizing side effects, becomes a new requirement in the field of drug delivery. In the recent few decades, a great many advancements of polymer synthetic methods have led to a new generation of bioactive polymers’ applications as drug controlled release carriers. In this review, we focus on the use of bioactive polymers for drug delivery system, with a particular in the utility of DNA-based nanocarriers and cell-penetrating peptides (CCPs)-based nanocarriers to provide precision control for drug …targeting or stimuli responsive systems. Show more

Keywords: DNA, cell-penetrating peptides, nanocarriers, drug delivery systems, targeting

DOI: 10.3233/BME-171648

Citation: Bio-Medical Materials and Engineering, vol. 28, no. s1, pp. S255-S261, 2017